We are performing CSF proteomics to identify early biomarkers for neurodegenerative disease using LC–MS/MS. Despite following standardized protocols, we are facing reproducibility and biological interpretation issues.
- Poor overlap of differentially expressed proteins between discovery and validation cohorts, even when using targeted MS.
- Ambiguous biological relevance, where statistically significant proteins lack clear mechanistic links to CNS pathology
Would alternative approaches (e.g., DIA-MS, extracellular vesicle enrichment, PTM-focused proteomics, or single-molecule methods) provide more reproducible insights?
What minimum standards should be enforced for CSF handling to improve cross-study comparability?
Thanks in advance